Myocardial infarction, especially if large and transmural, results in alterations in ventricular structure involving both the infarcted and noninfarcted myocardium. These alterations, which have been termed "ventricular remodeling," affect ventricular performance and survival. Compared to younger patients, the aged have more left ventricular dysfunction and worse long-term survival. The explanation for this is not clear. However, data in the senescent rat and in the pressure- and volume-overloaded aged rat suggest that compensatory myocardial hypertrophy sufficient to normalize wall stress is the major determinant of ventricular remodeling and function. We have preliminary data in aged rats which shows that, compared to younger rats, aged rats with the same size infarctions have more ventricular dilatation and less hypertrophy in the noninfarcted myocardium. These data support our hypothesis that: "In aged rats, inadequate compensatory hypertrophy of the noninfarcted myocardium results in extensive remodeling and deterioration in left ventricular function." This proposal outlines a novel approach to improving ventricular function by augmenting hypertrophy in the noninfarcted myocardium. The hypothesis is that this hypertrophy will reduce the extent of ventricular remodeling and its sequelae, i.e., ventricular dilatation, LV dysfunction, and increased mortality. The coronary artery ligation model of myocardial infarction will be used in 8 and 18 month old 344 X BN rats. One month after infarction, we will examine global cardiac function and analyze anatomic-morphologic components of left ventricular geometry to assess wall stress and remodeling. To create hypertrophy in the noninfarcted myocardium, we will use agents that inhibit fatty acid oxidation or that stimulate glucose (lactate) oxidation. The first agent will be tetradecylglycidic acid (TDGA), which we have shown will cause hypertrophy in the noninfarcted myocardium of normal Sprague-Dawley rats. This approach is designed to alter the process of ventricular remodeling post-infarction in the aged.